Canadian researchers have identified a genetic marker that can be detected through a blood test that determines which patients with metastatic colorectal cancer will benefit from receiving the epidermal growth factor receptor (EGFR) inhibitor cetuximab. This new study sheds light on the growing mystery of why cetuximab is ineffective for up to 50% of colorectal cancer patients.
"Our research discovered that the blood marker FCGR2A identifies a new group of patients that will benefit from taking cetuximab,” explained lead study author Geoffrey Liu, M.D., senior scientist at Princess Margaret Cancer Centre, University Health Network in Ontario. “With this finding, we believe we are now on the way to move it into the clinical setting to provide patients targeted, effective treatment."
This new study builds on some initial research done using the chimeric monoclonal antibody therapeutic to treat colorectal cancer patients almost ten years ago. However, it wasn’t until more recently when researchers began to discover that some patients seemed completely unaffected by the therapy that many research groups set out to find the underlying molecular mechanisms regulating this resistant behavior.
"In a group of metastatic colorectal cancer patients who were running out of treatment options, the previous clinical trial determined that cetuximab was most effective in a certain group of patients with tumors carrying a RAS mutation,” noted Dr. Liu. “But it certainly didn't work for everyone, and so the race was on to find out how to better identify which patients would benefit from this drug."
The findings from this study were published recently in Clinical Cancer Research through an article entitled “Fc-γ Receptor Polymorphisms, Cetuximab Therapy, and Survival in the NCIC CTG CO.17 Trial of Colorectal Cancer.”
“Our finding, which resulted from analyzing archived tumor and normal tissue samples from some of the 572 patients enrolled in that trial, further refines this quest and defines another subset of patients who will respond to the drug,” Dr. Liu remarked. "We need to find other ways to personalize cancer medicine for people with colorectal disease, keeping in mind that cetuximab is an expensive drug and can have side effects."
Dr. Liu continued that “instead of looking at aspects in the tumor, which is where RAS mutations show up, we looked at certain things in the blood and normal tissues that we could measure for heritable genetic variations."
Dr. Liu, a medical oncologist who specializes in lung cancer, describes the pathway to his team’s discovery as an ideal example of what can happen when you monitor the drug to wherever the research may lead.
"When we followed the drug, first in lung cancer and then in other cancers, it led us to colorectal cancer where the drug was also being used, and directly onto this new finding," Dr. Liu concluded.